Neurological ion channel disorders are Mendelian disorders caused by mutations in genes that encode ion channel subunits. Two broad groups exist: Skeletal muscle and neuronal channelopathies. As a member of CINCH (Consortium for the Clinical Investigation of Neurological Channelopathies), the MRC Centre for Neuromuscular Diseases is involved in the first ever large scale multicentre natural history trials of the nondystrophic myotonias (NDM), Andersen-Tawil syndrome (ATS) and the episodic ataxias (EAs). The trials aim to address three key areas: genotype-phenotype correlations; observe disease progression and evaluate investigations used in diagnosis. Our preliminary data point to a number of important findings: each of the neurological channelopathies is associated with a wide spectrum of clinical features; each exhibits considerable genetic heterogeneity; the absence of mutations in a few individuals suggests that other new genes are likely to underlie these disorders underpinning the importance of locus heterogeneity in ion channelopathies; and finally neurophysiological testing has an important role to play in the diagnosis of the skeletal muscle channelopathies. The results of these natural history trials will ultimately lead to a better understanding of the clinical features associated with specific genetic defects, improve diagnosis, and allow the assessment of endpoints for future treatment trials of these rare disorders.